# Adaptogenic Effects of Mushroom Blend Supplementation on Stress, Fatigue, and Sleep: A Randomised, Double‐Blind, and Placebo‐Controlled Trial

**Authors:** Ahmad Safiyyu'd‐din Hisamuddin, Faiqah Ramli, Teik Kee Leo, Mohamad Shazeli Che Zain, Mei Szin Wong, Mohd Raili Suhaili, Le Jie Lee, Tze Yan Lee

PMC · DOI: 10.1002/brb3.71193 · Brain and Behavior · 2026-01-15

## TL;DR

A 12-week trial found that Restake mushroom blend supplementation reduced stress, anxiety, fatigue, and improved sleep in stressed adults.

## Contribution

This is the first randomized, placebo-controlled trial showing adaptogenic effects of a mushroom blend on stress-related symptoms and biomarkers.

## Key findings

- Restake significantly reduced anxiety, depression, and fatigue compared to placebo.
- Supplementation improved sleep quality and lowered stress biomarkers like cortisol and CRP.
- Melatonin levels showed an increasing trend, suggesting improved circadian regulation.

## Abstract

Medicinal mushrooms have been gaining increasing attention as functional foods; however, scientific evidence from human studies remains limited.

In this study, 50 participants were randomly assigned to receive either Restake or a placebo. Psychological and physiological parameters were assessed at baseline, 6 weeks, and 12 weeks using validated tools, including the Pittsburgh Sleep Quality Index (PSQI), Visual Analog Scale for Fatigue (VAS‐F), Multidimensional Fatigue Inventory (MFI), State‐Trait Anxiety Inventory (STAI‐S), Perceived Stress Scale (PSS), Hamilton Anxiety Scale (HAM‐A), and Beck Depression Inventory (BDI). Serum biomarkers—cortisol, norepinephrine (NE), melatonin, adrenocorticotropic hormone (ACTH), and C‐reactive protein (CRP)—were analyzed via ELISA.

Anxiety, assessed by STAI‐S and HAM‐A, showed greater reductions in the Restake group at both 6 weeks (STAI‐S: p = 0.025; HAM‐A: p = 0.002) and 12 weeks (STAI‐S: p = 0.011; HAM‐A: p = 0.002). Depression (BDI) scores significantly decreased at 6 weeks (p < 0.001) and 12 weeks (p = 0.008). Fatigue levels showed significant reductions in general fatigue (p = 0.043), physical fatigue (p = 0.027), and mental fatigue (p = 0.043). Restake supplementation led to reductions in sleep quality scores (PSQI) at 6 weeks (p = 0.005) and 12 weeks (p < 0.001). Biomarker analysis revealed significant reductions (p < 0.001) in cortisol and ACTH levels and a decrease in CRP levels (p = 0.042). NE levels significantly (p = 0.033). Compared to the placebo group, Restake supplementation exhibited an increased morning melatonin trend after 12 weeks of intervention.

Restake supplementation was well tolerated and effectively reduced psychological stress, fatigue, and improved sleep quality without adverse effects.

In a randomized, double‐blind, placebo‐controlled trial, 50 moderately to severely stressed adults received Restake or placebo for 12 weeks. Psychological outcomes, including anxiety, depression, fatigue, perceived stress, and sleep quality, were evaluated alongside stress‐related biomarkers. Restake supplementation significantly reduced anxiety, depression, and multiple fatigue domains, while improving sleep quality over time. Biomarker analysis showed reductions in cortisol, adrenocorticotropic hormone, norepinephrine, and C‐reactive protein, with an increasing trend in morning melatonin levels. The intervention was well tolerated, supporting the potential role of medicinal mushroom supplementation in managing stress‐related symptoms and inflammation.

## Linked entities

- **Chemicals:** cortisol (PubChem CID 5754), norepinephrine (PubChem CID 951), melatonin (PubChem CID 896)

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}
- **Diseases:** Fatigue (MESH:D005221), Anxiety (MESH:D001007), Depression (MESH:D003866)
- **Chemicals:** melatonin (MESH:D008550), Restake (-), cortisol (MESH:D006854), NE (MESH:D009638)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12808922/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12808922/full.md

## References

64 references — full list in the complete paper: https://tomesphere.com/paper/PMC12808922/full.md

---
Source: https://tomesphere.com/paper/PMC12808922